This proposal has been modified over the past few years and has broadened to encompass the scope of a Clinical Psychopharmacology Research Program. The work of this unit currently is centered around five areas of investigation. The exploration of the dopamine hypothesis in relation to schizophrenia, the examination of aminergic theories underlying the etiology and treatment of the affective disorders. A continuation of work in regard to possible relationships between blood levels of psychotropic drugs, their metabolites and clinical response and incidence of side effects is proposed. The fourth area has been to initiate psychopharmacologic studies in geriatric subjects. Fifth, is the exploration of preclinical-clinical correlations. This work has derived from laboratory pharmacological or neurochemical studies which have been explored with the goal of predicting clinical activity of central acting agents. Finally, this program provides the ability to follow up leads that develop from various ongoing studies. This is perhaps as important a function as any of the aforementioned specific projects. The clinical psychopharmacology research unit is housed on ward PQ3 within the NYU-Bellevue Medical complex. The ward space has now been expanded to provide the unit accommodation for up to 32 research patients. This is a significant increase upon our prior capacity. Within this frame, careful clinical evaluation of psychoactive agents will be carried out. Agents will be selected that have had their pharmacological profile established in preclinical studies and where their effects and/or the structure of the compound provides us with a useful investigational tool to explore relevant clinical effects. This research requires the utilization of procedures that will guarantee the safety of the patient and also make it possible to study all aspects of drug action and to obtain detailed information about the clinical pharmacology and toxicological profile of these agents. These evaluations are made by utilizing a battery of quantitative rating devices and obtaining assessments from psychiatrist, psychologist, nurses, and patients. Initial pilot evaluations as well as double-blind controlled studies are carried out. BIBLIOGRAPHIC REFERENCES: Shopsin, B. Tryptophan and allopurinol in the treatment of depression. Lancet No. 7970, Vol. 1, p. 1189, May 29, 1976.